The Lymph Node Ratio is the Strongest Prognostic Factor after Resection of Pancreatic Cancer

Introduction  Survival after surgery of pancreatic cancer is still poor, even after curative resection. Some prognostic factors like the status of the resection margin, lymph node (LN) status, or tumor grading have been identified. However, only few data have been published regarding the prognostic influence of the LN ratio (number of LN involved to number of examined LN). We, therefore, evaluated potential prognostic factors in 182 patients after resection of pancreatic cancer including assessment of LN ratio. Methods  Since 1994, 204 patients underwent pancreatic resection for ductal pancreatic adenocarcinoma. Survival was evaluated in 182 patients with complete follow-up evaluations. Of those 182 patients, 88% had cancer of the pancreatic head, 5% of the body, and 7% of the pancreatic tail. Patients underwent pancreatoduodenectomy (85%), distal resection (12%), or total pancreatectomy (3%). Survival was analyzed by the Kaplan–Meier and Cox methods. Results  In all 204 resected patients, operative mortality was 3.9% (n = 8). In the 182 patients with follow-up, 70% had free resection margins, 62% had G1- or G2-classified tumors, and 70% positive LN. Median tumor size was 30 (7–80) mm. The median number of examined LN was 16 and median number of involved LN 1 (range 0–22). Median LN ratio was 0.1 (0–0.79). Cumulative 5-year survival (5-year SV) in all patients was 15%. In univariate analysis, a LN ratio ≥ 0.2 (5-year SV 6% vs. 19% with LN ratio < 0.2; p = 0.003), LN ratio ≥ 0.3 (5-year SV 0% vs. 18% with LN ratio < 0.3; p < 0.001), a positive resection margin (p < 0.01) and poor differentiation (G3/G4; p < 0.03) were associated with poorer survival. In multivariate analysis, a LN ratio ≥ 0.2 (p < 0.02; relative risk RR 1.6), LN ratio ≥ 0.3 (p < 0.001; RR 2.2), positive margins (p < 0.02; RR 1.7), and poor differentiation (p < 0.03; RR 1.5) were independent factors predicting a poorer outcome. The conventional nodal status or the number of examined nodes (in all patients and in the subgroups of node positive or negative patients) had no significant influence on survival. Patients with one metastatic LN had the same outcome as patients with negative nodes, but prognosis decreased significantly in patients with two or more LN involved. Conclusions  Not the lymph node involvement per se but especially the LN ratio is an independent prognostic factor after resection of pancreatic cancers. In our series, the LN ratio was even the strongest predictor of survival. The routine estimation of the LN ratio may be helpful not only for the individual prediction of prognosis but also for the indication of adjuvant therapy and herein related outcome and therapy studies. Presented in part at the 49th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 2008 in San Diego and at the Annual Meeting of the German Cancer Society, February 2008 in Berlin, Germany     

Preoperative Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor after Curative Resection for Hepatocellular Carcinoma

BACKGROUND: This study was designed to evaluate the impact of an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) on outcome after curative resection for hepatocellular carcinoma (HCC). METHODS: Patients undergoing resection for HCC from January 1994 to May 2007 were identified from the hepatobiliary database. Demographics, laboratory analyses, and histopathology data were analyzed. RESULTS: A total of 96 patients were identified with a median age at diagnosis of 65 (range, 15-85) years. The 1-, 3-, and 5-year overall survival rates were 80%, 58%, and 52%, respectively. Although the presence of microvascular invasion, NLR >or=5, and R1 resection margin were adverse predictors of overall survival, there were no independent predictors identified on multivariate analysis. The 1-, 3-, and 5-year disease-free survival rates were 74%, 63%, and 57%, respectively. Preoperative tumor biopsy, NLR >or= 5, multiple liver tumors, microvascular invasion, and R1 resection margin were all predictors of poorer disease-free survival. Multivariate analysis showed that a NLR >or= 5 and R1 resection margin were independent predictors of poorer disease-free survival. The median disease-free survival of those with a NLR >or= 5 was 8 months compared with 18 months for those with a NLR < 5. CONCLUSION: Preoperative NLR >or= 5 was an adverse predictor of disease-free and overall survival.     

Prognostic Significance of Complications after Curative Surgery for Gastric Cancer

Background

Postoperative complications such as anastomotic leakage were reported to be a major independent prognostic factor for long-term survival in gastrointestinal malignancies. This study sought to clarify the prognostic significance of postoperative inflammatory complications specifically for patients with gastric cancer.

Methods

This study included 1,395 patients who underwent curative resection for gastric cancer from 2005 to 2008. Complications were evaluated according to the Clavien-Dindo classification. Overall survival (OS) and disease-specific mortality (DSM) were compared between complication and no-complication groups. Presence of complications was modeled by the Cox proportional hazard model for OS and the Fine and Gray competing risk regression model for DSM to assess the correlation between complication and prognosis.

Results

The median follow-up time was 3.1 years. Two hundred seven patients (14.8 %) had complications of grade 2 or higher. Of 131 patients who died within this period, 87 died of gastric cancer. The 3-year OS in the complication group was 84.1 % compared to 93.1 % in the no-complication group (P < 0.0001). The cumulative incidence of DSM was also significantly worse in patients with complications (P < 0.0001). Multivariate analysis identified the same significant increasing risk of complication for both OS (hazard ratio 1.88; 95 % confidence interval 1.26–2.80) and DSM (hazard ratio 1.90; 95 % confidence interval 1.19–3.02).

Conclusions

Postoperative complications that can cause prolonged inflammation have an obvious impact not only on the OS but also on the DSM of patients with gastric cancer even if the tumor is resected curatively.     

Positive Lymph Node Ratio Is an Independent Prognostic Factor in Gastric Cancer After D2 Resection Regardless of the Examined Number of Lymph Nodes

The purpose of this study was to clarify the outcome of the ratio between metastatic and examined lymph nodes (N ratio) in gastric cancer patients with ≤15 examined lymph nodes after D2 lymphadenectomy. A retrospective study was performed in 906 patients with gastric cancer who had undergone D2 resection. Patients with ≤15 examined lymph nodes (group 1, n = 729) and those with >15 lymph nodes (group 2, n = 177) were analyzed separately. N ratio categories were identified as follows: N ratio 0, 0%; N ratio 1, 1% to 9%; N ratio 2, 10% to 25%; N ratio 3, >25%. Univariate analysis found that both the tumor, node, metastasis system (N staging system) and N ratio system well classified patients with significantly different prognosis. By multivariate analysis, only the N ratio classification was retained as an independent prognostic factor in both group 1 and 2 compared with the N stage system. Furthermore, when patients were divided into four groups according to the number of lymph nodes examined (1 to 3, 4 to 7, 8 to 11, and 12 to 15), the 5-year survival rates remained similar between groups according to the same N ratio (p > .05). Positive N ratio classification is a better prognostic tool compared with N staging system after D2 resection in patients with gastric cancer. It can prevent stage migration and can be used regardless of the examined number of lymph nodes. Da-zhi Xu and Qi-rong Geng contributed equally to this work.     

Benefit of Post-operative Surveillance for Recurrence after Curative Resection for Gastric Cancer

Background  

Although most clinicians perform surveillance after gastrectomy, there is no consensus on the optimal follow-up schedule. This study aimed to evaluate the benefit of postoperative surveillance for recurrence after curative resection for gastric cancer.     

Prognostic Significance of the Metastatic Lymph Node Ratio in Gastric Cancer Patients

Background  

Lymph node metastasis is considered one of the most important prognostic factors in gastric cancer. However, the optimal system for accurate staging of lymph node metastasis for patients with gastric cancer remains controversial. This study was designed to investigate the prognostic significance of the metastatic lymph node ratio (MLR), which is calculated by dividing the number of metastatic lymph nodes by the total number of nodes harvested from patients with gastric cancer.     

Prognostic Significance of Metastatic Lymph Node Ratio in T3Gastric Cancer

The fifth International Union Against Cancer tumor node metastasis (UICC TNM) classification, based on the number of metastatic lymph nodes (LN), has proved to be a reliable and objective method for predicting the prognosis of patients with gastric cancer. However, the prognosis of patients with T3 gastric cancer is still heterogeneous. This study was carried out to investigate the validity of metastatic LN ratio as a prognostic factor in T3 gastric cancer. A retrospective analysis was performed on a total of 833 patients that had either T3N1M0 (n = 504) or T3N2M0 (n = 329) gastric cancer by the fifth UICC classification. A preliminary analysis revealed the cutoff values for T3N1M0 to be 10% and for T3N2M0 to be 25%. The mean metastatic LN ratio was 9.0% for T3N1M0 cancer and 26.9% for T3N2M0 cancer. For the T3N1M0 stage, the patients who showed less than 10% of the metastatic LN ratio were grouped as N1-low with the others grouped as N1-high. For the T3N2M0 stage group, those who had less than 25% of the metastatic LN ratio were grouped as N2-low, the remainder as N2-high. The metastatic LN ratio decreased in proportion to the extent of lymphadenectomy and it increased in relation to the increasing scale of the fourth N classification. The rates of recurrence were significantly different according to the metastatic LN ratio in N1 and N2 classification of the fifth UICC classification (p < 0.05). The 5-year survival rates after gastrectomy decreased significantly by increasing the metastatic LN ratio in both T3N1M0 cancers (p =0.0026) and T3N2M0 cancers (p = 0.0057). The metastatic LN ratio was an independent risk factor for recurrence and poor prognosis. Our data suggest that the metastatic LN ratio is a significant prognostic factor for T3 gastric cancer. Furthermore, the application of the metastatic LN ratio can provide information not only about the extent of LN metastasis but also about the extent of lymphadenectomy in T3 gastric cancer.     

Prognostic Significance of Microscopic Positive Margins for Gastric Cancer Patients with Potentially Curative Resection

Background  

Most previous studies concerning the impact of positive margins on patient outcomes were based on patients with D1 lymphadenectomy. The prognostic significance of positive margins for patients with D2/D3 lymphadenectomy has not been investigated.     

Sarcopenia is a Negative Prognostic Factor After Curative Resection of Colorectal Cancer

Annals of Surgical Oncology - Skeletal muscle depletion (sarcopenia) is closely associated with limited physical ability and high mortality. This study was performed to evaluate the prognostic...     

Detection of Lymph Node Involvement by Cytokeratin Immunohistochemistry is an Independent Prognostic Factor After Curative Resection of Esophageal Cancer

Background  

Involved lymph nodes (LN) are a negative prognostic factor in esophageal cancers. To assess the role of nodal micrometastases, we performed immunohistochemical analyses of LN after resection of node-negative esophageal cancers and correlated the results with survival.     

Prognostic Relevance of Lymph Node Ratio and Number of Resected Nodes after Curative Resection of Ampulla of Vater Carcinoma

Background  Nodal metastasis is considered a major prognostic factor in patients with ampulla of Vater carcinoma (AVC). No study has investigated the significance of the ratio between metastatic and resected/examined lymph nodes (LNR) in patients with AVC. Methods  Demographic, operative, and pathology data, including number of resected/evaluated nodes and LNR, were collected from patients who underwent pancreaticoduodenectomy with radical intent for invasive AVC from 1990 to 2005. Survival rates and recurrence patterns were evaluated and predictors were identified. Results  In 90 evaluable patients (51 males, 39 females, median age 62.5 years), 5-year disease-specific survival (DSS) was 61%. The median number of resected/evaluated nodes was 16 (range: 5–47); 50% of the patients had nodal metastases. The 5-year DSS according to LNR was 75%, 49%, 38%, and 0% for LNR = 0, LNR >0 and ≤0.2, LNR >0.2, and ≤0.4, and LNR >0.4 (P = 0.002), respectively. The 5-year DSS was 81% in patients with >16 resected/evaluated nodes compared with 45% in those with ≤16 resected/evaluated nodes (P = 0.001). On multivariate analysis LNR and a number of resected/evaluated nodes >16 were significant predictors of survival; a number of resected/evaluated nodes >16 was also the only independent predictor of recurrence. Conclusions  After curative resection for AVC, LNR and a cutoff of 16 resected/evaluated nodes are powerful prognostic factors. LNR might represent a major parameter for patient stratification in adjuvant treatment trials.     

Appropriate Gastric Resection with Lymph Node Dissection for Early Gastric Cancer

Background The extent of lymphadenectomy (limited vs. extended) and that of gastric resection (partial vs. total) remain controversial issues in the management of early gastric cancer (EGC). A multicentric study was performed to elucidate the appropriate gastric resection with lymph node dissection for early gastric cancer.Methods From 1979 to 1988, 332 patients with EGC underwent surgery in 23 French centers. Clinicopathological data, the extent of resection, and the number of lymph nodes retrieved were reviewed retrospectively and screened for prognostic effect. The mean follow-up for the 332 EGC patients was 80 months.Results Postoperative mortality was correlated to age (odds ratio [OR], 1.1) and extent of gastric resection (OR,10.3). Examination of survival data (excluding postoperative deaths) with univariate analysis and the Cox proportional hazards model showed that the independent factors for excellent prognosis included no lymphatic involvement (P = .005), 10 or more lymph nodes retrieved (P = .003), site of the tumor in the lower third of the stomach (P = .01), and mucosal lesions (P = .04). The extent of resection did not influence long-term survival.Conclusions Our results suggest that because of the associated good prognosis, the appropriate surgical treatment for EGC is partial gastrectomy with lymphadenectomy retrieving 10 or more lymph nodes.     

Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio Are Not Prognostic Biomarkers in Rectal Cancer Patients with Curative Resection

Background

Actual predictors of survival and recurrence for rectal cancer patients undergoing curative resection mostly come from pathological data of surgical specimen. Recently, novel blood biomarkers have been proposed as useful tools in cancer patient management, but few and conflicting data have been reported in rectal cancer. We evaluated the prognostic relevance of preoperative platelet-to-lymphocyte (P/L) ratio and neutrophil-to-lymphocyte (N/L) ratio on survival and recurrence in patients undergoing laparoscopic curative resection for rectal cancer.

Methods

All consecutive patients who referred for primary rectal disease to the Department of General Surgery in Cittadella (Italy) from June 2005 to September 2015 were retrospectively evaluated. Patients with metastatic disease at surgery were excluded. P/L and N/L ratios were calculated. For patients undergoing neoadjuvant chemo-radiotherapy, pre-treatment data were considered. Follow-up data were updated at December 2016.

Results

One hundred fifty-two patients were included in the study, 49 (32%) received neoadjuvant chemo-radiotherapy. Both P/L and N/L ratios showed poor discriminative performance on 5-year OS and DFS. Time-dependent ROC curves showed no improvements in discriminative performance of P/L and N/L ratios when considering different time endpoints. Multivariable analysis identified CEA—rather than P/L or N/L ratios—as independent predictor of OS and DFS, adjusting for age, tumor stage, and postoperative morbidity.

Conclusion

Neither P/L nor N/L ratios were associated with survival after rectal cancer surgery. Further studies on large series might provide insights on the role of these inexpensive blood biomarkers in rectal cancer.

     

Prognostic Impact of Microscopic Tumor Involved Resection Margin in Advanced Gastric Cancer Patients after Gastric Resection

Background

The prognosis of patients with positive surgical resection margins is dismal in gastric cancer. However, the influence of positive margin itself on prognosis is still uncertain, especially in advanced gastric cancer (AGC). The aims of the present study were to evaluate the prognostic impact of microscopic tumor involved resection margins in stage III–IV AGC after gastric resection in comparison with other well-known factors.

Methods

Among 1,536 consecutive gastric cancer patients who received intentional curative resection for stage III–IV AGC between April 2001 and December 2011 at the National Cancer Center, 35 patients (2.28 %) had positive resection margins on their final histology. A comparison of clinicopathologic characteristics, recurrence pattern, overall survival (OS), and disease-free survival (DFS) was made between positive margin (PM) patients and negative margin (NM) patients.

Results

Among the 35 PM patients, 15 (42.9 %) had proximal involved margins, 21 (60.0 %) had distal involved margins, and one (2.9 %) had both involved margins. Twenty-eight PM patients (80.0 %) were stage III, and 7 (20.0 %) were stage IV. Recurrence was significantly higher in PM than NM (63.6 % vs. 39.7 %, respectively; p = 0.005). The OS and DFS rates were significantly lower in the PM group than in the NM group (14.9 vs. 36.3 months, p < 0.001 and 11.6 vs. 27.1 months, p = 0.005, respectively). The presence of PM was an independent risk factor for both OS and DFS.

Conclusions

The presence of PM is an independent risk factor for OS and DFS. Considering the prognostic impact of PM, a sufficient resection margin should be ensured when determining the resection line in gastrectomy with curative intent. The reoperation to secure clear resection margins should be considered as a treatment of choice in the case of PM.     

Prognostic Factors for Survival in Patients with Hepatic Recurrence After Curative Resection of Gastric Cancer

Background  This study was done to evaluate the prognostic factors that may affect the survival of patients with recurrent hepatic metastasis after curative resection of gastric cancer. Methods  We reviewed the medical records of 73 patients with recurrent hepatic metastasis after surgical treatment of gastric cancer from January 1995 to December 2005. Prognostic factors were classified into three groups: primary tumor factors, recurrent hepatic factors, and treatment factors. The prognostic values of these factors were assessed using univariate and multivariate analyses by the log-rank test in the Kaplan-Meier method and Cox’s proportional hazard model. Results  The overall median survival rate of the 73 study patients was 20.0 months [95% confidence interval (CI) 15.4–24.6 months]. The median survival rate after diagnosis of recurrent hepatic metastasis was 5 months (95% CI 3.5–6.5 months). Univariate analysis showed that the favorable prognostic factors were stage I and II among the primary tumor factors, no extrahepatic metastasis and unilobar distribution among the recurrent hepatic factors, and radiofrequency ablation (RFA) ± chemotherapy among the treatment factors when operative treatment had been excluded. The independent favorable prognostic factors revealed by the multivariate analysis were no extrahepatic metastasis and RFA ± chemotherapy. The median survival rate of patients who had two favorable prognostic factors was 27 months (95% CI 0–66.38 months). Conclusions  Improvement in the survival rate can be expected with RFA ± chemotherapy for patients with recurrent gastric cancer in the liver without extrahepatic metastasis.     

Prognostic Significance of the Metastatic Lymph Node Ratio in Patients with Gastric Cancer

Background  

In gastric cancer, the classification of lymph node status is still a controversial prognostic factor. Recent studies have proposed a new prognostic factor (metastatic lymph node ratio: MLR) for gastric cancer patients who undergo curative resection. The present study tested the hypothesis that MLR was better than the current pN staging system by analyzing the correlation between MLR and the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system, by analyzing the correlation between MLR and 5-year overall survival (OS), by comparing area under the curve (AUC), and by performing univariate and multivariate analyses for OS.     

The Lymph Node Ratio Is a Powerful Prognostic Factor of Node-Positive Colon Cancers Undergoing Potentially Curative Surgery

Background  

The number of harvested (LNs) and metastatic nodes (LNs+) represents the most significant factor to define postoperative treatment and prognosis in colon cancer. However, its assessment may be inadequate causing an incorrect cancer staging. The lymph node ratio (LNR: the ratio between metastatic and resected nodes) has shown prognostic significance in many tumors; however, its role in colon cancer is not clearly elucidated. This study investigated LNR as a prognostic factor in node-positive colon cancers.     

Improvement of Operative Mortality after Curative Resection for Gastric Cancer: Population-based Study

It is not well known if the improvement in operative mortality after surgery for gastric cancer reported in hospital series can be extrapolated to the whole population. The aim of this study was to determine trends in operative mortality over a 20-year period in a nonselected community-based series of patients. A database of 648 patients with gastric cancer resected with curative intent between 1976 and 1995 in a region with a half-million population was divided into two periods: 1976–1983 and 1984–1995. Nonconditional logistic regression was performed to estimate the independent effects of the studied factors. Operative mortality was higher during the 1976–1983 period than during the 1984–1995 period (17.1% vs. 7.1%; p < 0.0001). When comparing the two study periods, operative mortality decreased dramatically from 26.2% to 10.0% in patients over age 70, from 31.8% to 7.9% after total gastrectomy, and from 30.7% to 6.3% after proximal esophagogastrectomy. Operative mortality after total gastrectomy was nearly the same as that after distal gastrectomy (7.9% vs 5.9%) during the second study period. During the first study period, operative mortality was independently associated with age at diagnosis, type of gastrectomy, and to a lesser degree stage at diagnosis; during the second study period, only age and stage at diagnosis were associated with the risk of operative mortality. This study indicates that in this well defined population operative mortality after curative resection for gastric cancer has decreased during the last 20 years. The results should encourage aggressive management of patients with gastric cancer, even in patients over 70 years of age.